Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are the preferred drugs to treat hypercholesterolemia, an established risk factor for cardiovascular disease. Although statins are effective in inhibiting cholesterol synthesis and reducing blood levels, their use is associated with a variety of muscle related-complaints, including pain and fatigue, which can affect quality of life and compliance with medications. Since the efficacy of statins on preventing cardiovascular disease has been demonstrated, the means of ensuring their continued use is clinically very important. Statin-induced muscle symptoms may, in part, be a consequence of a mitochondrial deficit resulting from the inhibition of synthesis of coenzyme Q10 (coQ10), an essential cofactor for mitochondrial electron transport systems, which shares the same biosynthetic pathway as cholesterol. CoQ10 deficiency could impair oxidative phosphorylation and mitochondrial energy production, thus affecting muscle metabolism and function. This hypothesis is supported by the results of our pilot study demonstrating that muscle pain associated with statin use can be significantly reduced with coQ10 supplementation for 30 days. This project will evaluate the ability of supplementation with coQ10 to improve mitochondrial oxidative capacity and muscle function and reduce muscle-related side effects associated with statin use. It will also investigate the molecular mechanisms responsible for beneficial effects of coQ10 supplementation. In double-blind trials, myopathic symptoms, their interference with daily activities, aerobic capacity, and muscle function will be assessed before and after supplementation with either coQ10 or placebo in groups of statin-treated subjects complaining of myopathic symptoms. The mechanisms associated with improvement of muscle symptoms and function after supplementation with coQ10 will be also evaluated by measuring the changes in the activity of mitochondrial enzymes involved in the oxidative metabolism, i.e. the enzymes of the mitochondrial respiratory chain. Therefore, this project corresponds precisely to the NCCAM mission for early phase clinical studies of CAM approaches to the prevention of cardiovascular disease. PUBLIC HEALTH RELEVANCE: Over 17 million patients are currently treated with statins for lowering blood cholesterol levels to prevent cardiovascular disease. The ability of supplementation with coQ10 to improve muscle energy production and reduce muscle-related side effects associated with statin use has the potential to impact significantly on the risk of cardiovascular disease, the leading cause of death in the U.S.